Cancer stem cells, found in many types of cancer, are rare
populations of malignant cells with the capacity for endless
self-renewal. They are believed to be responsible for tumor growth,
recurrence and metastasis. Their resistance to chemotherapy and
conventional anti-cancer agents make them important targets for
novel therapies.

“These data are significant because they demonstrate that
the cancer stem cell population can be targeted by inhibiting
telomerase with imetelstat, and that this is associated with a
survival benefit in animal models,” said Stephen M. Kelsey,
M.D., Geron's executive vice president and chief medical officer,
oncology. “Our Phase 2 clinical program is testing imetelstat
in lung cancer, chronic leukemias, breast cancer and multiple
myeloma, all malignancies in which cancer stem cells are believed
to play an important role in relapse after standard
therapy.”

Multiple Myeloma

The first publication shows the inhibitory effect of imetelstat
on multiple myeloma cancer stem cells in vitro and in animal
models of the human disease. The research, published in the journal
PLoS ONE, was co-authored by Dr. William Matsui and
colleagues at The Sidney Kimmel Comprehensive Cancer Center at
Johns Hopkins and scientists from Geron. The publication is
available online at
http://dx.plos.org/10.1371/journal.pone.0012487.

The data demonstrate that treatment with the telomerase
inhibitor, imetelstat, for two weeks in vivo in a xenograft
model of established human multiple myeloma resulted in significant
survival benefit compared to controls: 8/8 animals alive in the
imetelstat treated group versus 0/8 alive in the control group at
day 110.

To determine if the survival benefit was due to targeting of the
cancer stem cells, further in vitro and in vivo
experiments using cancer stem cells isolated from human multiple
myeloma cell lines and primary myeloma patient samples were
performed. Cancer stem cells isolated from human multiple myeloma
cell lines and treated with imetelstat in vitro showed
reduced proliferation with five-fold fewer colonies after treatment
for three weeks and 100-fold fewer colonies after five weeks
compared to controls. Importantly, similar results were obtained
using multiple myeloma stem cells isolated from samples of patient
bone marrow, demonstrating that cancer stem cells from the cell
lines are representative of the human disease.

Establishment of new tumors in a xenograft model serves as an
experimental model of disease recurrence. When myeloma cells were
pretreated in vitro with imetelstat for two weeks and
subsequently implanted in mice given no further treatment, the
development of new tumors was significantly reduced, leading to
increased survival of the animals compared to controls implanted
with untreated myeloma cells.

Breast and Pancreatic Cancer

The second publication demonstrates the inhibitory effect of
imetelstat on cancer stem cells from breast and pancreatic tumor
cell lines in vitro and in animal models of the human
disease. The data, published in the journal Cancer Research,
were co-authored by Geron scientists and Professors Jerry Shay and
Woodring Wright at the University of Texas Southwestern Medical
Center at Dallas. The abstract of the publication is available on
the journal's website at
http://cancerres.aacrjournals.org/content/early/2010/11/04/0008-5472.CAN-10-0233.abstract.

Treatment in vitro of pancreatic and breast cancer cell
lines with imetelstat reduced the proportion of cancer stem cells
from the bulk tumor populations by 1.6 to 12 fold in all cell lines
tested. In addition, imetelstat inhibited the growth of bulk breast
cancer cells, resulting in cell death after three weeks of
treatment.

A key in vitro characteristic of cancer stem cells is the
ability of single breast cancer stem cells to give rise to a sphere
of cells called mammospheres, which can subsequently give rise to
new mammospheres when dissociated. Imetelstat treatment resulted in
a two-fold reduction in the number of new mammospheres formed from
single cells and an 8-fold decrease in the number of cells in each
mammosphere compared to controls.

Xenograft studies were also performed to assess the impact of
imetelstat treatment on breast and pancreatic cancer stem cell
function in vivo. Breast or pancreatic cancer cell lines
were pre-treated with imetelstat in vitro and implanted into
mice. Imetelstat was also administered to these animals for an
additional 50 days. Control animals were implanted with untreated
cancer cell lines and then given saline. Imetelstat treatment
significantly reduced the frequency of tumor formation from
implanted pancreatic and breast cancer lines. As expected, tumors
were present at day 50 in all of the untreated control animals
implanted with pancreatic cancer cells. In contrast, only half of
the animals in the imetelstat-treated group had tumors. Similarly,
50 days after implanting the breast cancer cells, tumors were
present in 80% of the untreated control group, but in only 40% of
the imetelstat group.

Telomerase is a critical and broadly applicable tumor target.
The enzyme is expressed in a wide range of malignant tumors, and
its activity is essential for the indefinite replicative capacity
of cancer that enables malignant cell growth. Telomerase has now
also been shown to be a target for cancer stem cells. Telomerase is
absent or expressed only transiently at low levels in most normal
adult tissues.

Imetelstat is a lipidated short chain oligonucleotide that binds
with high affinity and specificity to the catalytic site of
telomerase, resulting in competitive inhibition of enzyme activity.
Proprietary manufacturing chemistry and the addition of a 5' lipid
chain have enabled the molecule to penetrate cells and tissues
throughout the body.

Imetelstat has been tested in six Geron-sponsored Phase 1
clinical trials at 22 U.S. medical centers treating over 180
patients examining the safety, tolerability, pharmacokinetics and
pharmacodynamics of the drug, alone or in combination with other
standard therapies, in patients with different hematological and
solid tumors.

A randomized Phase 2 clinical trial of imetelstat has been
initiated in non-small cell lung cancer. A second randomized Phase
2 trial is planned in breast cancer and two single arm Phase 2
clinical trials are planned in multiple myeloma and essential
thrombocythemia.

About Geron

Geron is developing first-in-class biopharmaceuticals for the
treatment of cancer and chronic degenerative diseases, including
spinal cord injury, heart failure and diabetes. The company is
advancing an anti-cancer drug and a cancer vaccine that target the
enzyme telomerase through multiple clinical trials in different
cancers. For more information, visit
www.geron.com.

This news release may contain forward-looking statements made
pursuant to the “safe harbor” provisions of the Private
Securities Litigation Reform Act of 1995. Investors are cautioned
that statements in this press release regarding potential
applications of Geron's telomerase technology constitute
forward-looking statements that involve risks and uncertainties,
including, without limitation, risks inherent in the development
and commercialization of potential products, uncertainty of
clinical trial results or regulatory approvals or clearances, need
for future capital, dependence upon collaborators and protection of
our intellectual property rights. Actual results may differ
materially from the results anticipated in these forward-looking
statements. Additional information on potential factors that could
affect our results and other risks and uncertainties are detailed
from time to time in Geron's periodic reports, including the
quarterly report on Form 10-Q for the quarter ended September 30,
2010.